Longitudinal Follow-up of Reproductive and Metabolic Features of Valproate-Associated Polycystic Ovarian Syndrome Features: A Preliminary Report

• Published in: Biological psychiatry (1969) 2006-12, Vol.60 (12), p.1378-1381
• Main Authors: Joffe, Hadine, Cohen, Lee S., Suppes, Trisha, Hwang, Cindy H., Molay, Francine, Adams, Judith M., Sachs, Gary S., Hall, Janet E.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Antimanic Agents - adverse effects; Antimanic Agents - therapeutic use; Biological and medical sciences; bipolar disorder; Bipolar Disorder - complications; Bipolar Disorder - drug therapy; Body Mass Index; Drug toxicity and drugs side effects treatment; Female; Follow-Up Studies; Hirsutism - chemically induced; Humans; Hyperandrogenism - chemically induced; longitudinal; Longitudinal Studies; Medical sciences; Metabolism - drug effects; Middle Aged; Overweight; PCOS; Pharmacology. Drug treatments; polycystic ovarian syndrome; Polycystic Ovary Syndrome - chemically induced; Polycystic Ovary Syndrome - complications; Polycystic Ovary Syndrome - metabolism; Reproduction - drug effects; Testosterone - blood; Toxicity: urogenital system; valproate; Valproic Acid - adverse effects; Valproic Acid - therapeutic use; Women
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2006.05.027

In the Systematic Treatment Enhancement Program for Bipolar Disorder, we showed that valproate is associated with new-onset menstrual-cycle irregularities and hyperandrogenism in 10.5% of 86 women. We now determine whether polycystic ovarian syndrome (PCOS) features reverse on valproate discontinutation. Women with valproate-associated PCOS and those at risk for PCOS (valproate use ≤6 months) were re-evaluated for PCOS. Follow-up (mean 17 months) assessments were completed in 14 women (5 with treatment-emergent PCOS, 9 on valproate ≤6-month). Of seven women who developed valproate-associated PCOS, PCOS reproductive features remitted in three of four discontinuing valproate and persisted in all 3 continuing valproate. Menstrual-cycle irregularities improved among valproate-discontinuers whose PCOS features remitted (p = 0.01). There was a trend toward lower serum testosterone (p = 0.06). Body-weight and polycystic ovarian morphology did not change. In the first longitudinal bipolar-disorder study of valproate-associated PCOS, most valproate-discontinuers had improved reproductive features of PCOS despite static body-weight.